Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model DOI Creative Commons

Suraj Singh Rawat,

Anand Kumar Keshri,

Naina Arora

и другие.

Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(5)

Опубликована: Май 1, 2024

Abstract The excretory–secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium . cysticerci T. causes infection the central nervous system known as neurocysticercosis (NCC), which affects significant population developing countries. Extracellular vesicles (EVs) are 30–150‐nm‐sized particles constitute part secretome. However, EV NCC pathogenesis remains undetermined. Here, for first time, we report that from larvae is abundant metabolites can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT mTOR degradation through auto‐lysosomal route with prominent increase ubiquitination proteins. This results less ROS production diminished bacterial killing capability among EV‐treated macrophages. Due this, macro‐autophagy caspase‐linked apoptosis upregulated, reduction autophagy substrate sequestome 1. In summary, viable cysts attenuates AKT–mTOR pathway thereby promoting macrophages, this may exert immunosuppression an early stage parasite NCC, primarily asymptomatic. Further investigation on EV‐mediated suppression revealed protect mice DSS‐induced colitis improve colon architecture. These findings shed light previously unknown therapeutic their potential.

Язык: Английский

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model DOI Creative Commons

Suraj Singh Rawat,

Anand Kumar Keshri,

Naina Arora

и другие.

Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(5)

Опубликована: Май 1, 2024

Abstract The excretory–secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium . cysticerci T. causes infection the central nervous system known as neurocysticercosis (NCC), which affects significant population developing countries. Extracellular vesicles (EVs) are 30–150‐nm‐sized particles constitute part secretome. However, EV NCC pathogenesis remains undetermined. Here, for first time, we report that from larvae is abundant metabolites can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT mTOR degradation through auto‐lysosomal route with prominent increase ubiquitination proteins. This results less ROS production diminished bacterial killing capability among EV‐treated macrophages. Due this, macro‐autophagy caspase‐linked apoptosis upregulated, reduction autophagy substrate sequestome 1. In summary, viable cysts attenuates AKT–mTOR pathway thereby promoting macrophages, this may exert immunosuppression an early stage parasite NCC, primarily asymptomatic. Further investigation on EV‐mediated suppression revealed protect mice DSS‐induced colitis improve colon architecture. These findings shed light previously unknown therapeutic their potential.

Язык: Английский

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